Association between coronary plaque volume and myocardial ischemia detected by dynamic perfusion CT imaging.

Introduction: We aimed to evaluate the relationship between quantitative plaque metrics derived from coronary CT angiography (CTA) and segmental myocardial ischemia using dynamic perfusion CT (DPCT). Methods: In a prospective single-center study, patients with > 30% stenosis on rest CTA underwent regadenoson stress DPCT. 480 myocardium segments of 30 patients were analyzed. Quantitative plaque assessment included total plaque volume (PV), area stenosis, and remodeling index (RI). High-risk plaque (HRP) was defined as low-attenuation plaque burden > 4% or RI > 1.1. Absolute myocardial blood flow (MBF) and relative MBF (MBFi: MBF/75th percentile of all MBF values) were quantified. Linear and logistic mixed models correcting for intra-patient clustering and clinical factors were used to evaluate the association between total PV, area stenosis, HRP and MBF or myocardial ischemia (MBF < 101 ml/100 g/min). Results: Median MBF and MBFi were 111 ml/100 g/min and 0.94, respectively. The number of ischemic segments were 164/480 (34.2%). Total PV of all feeding vessels of a given myocardial territory differed significantly between ischemic and non-ischemic myocardial segments (p = 0.001). Area stenosis and HRP features were not linked to MBF or MBFi (all p > 0.05). Increase in PV led to reduced MBF and MBFi after adjusting for risk factors including hypertension, diabetes, and statin use (per 10 mm3; ß = -0.035, p < 0.01 for MBF; ß = -0.0002, p < 0.01 for MBFi). Similarly, using multivariate logistic regression total PV was associated with ischemia (OR = 1.01, p = 0.033; per 10 mm3) after adjustments for clinical risk factors, area stenosis and HRP. Conclusion: Total PV was independently associated with myocardial ischemia based on MBF, while area stenosis and HRP were not.

Total coronary atherosclerotic plaque burden is associated with myocardial ischemia in non-obstructive coronary artery disease.

AIM: Whether the total coronary atherosclerotic plaque burden is independently associated with myocardial ischemia in non-obstructive coronary artery disease (CAD) is not well established. We aimed to test the association of total plaque burden quantified by coronary computed tomography angiography (CCTA) with myocardial ischemia in patients with chronic coronary syndrome and non-obstructive CAD. METHODS: We included 125 patients (age 62 ± 9 years, 58% women) with chronic coronary syndrome and non-obstructive CAD (stenosis < 50%) by CCTA, who were grouped according to presence or absence of myocardial ischemia by myocardial contrast stress echocardiography. Total plaque burden was quantified by CCTA as the total plaque volume in the main coronary arteries, and positive remodelling was defined as remodelling index > 1.10. RESULTS: Patients with myocardial ischemia (n = 66) had higher total plaque burden (847 ± 245 mm3 vs. 758 ± 251 mm3, p = 0.049) and higher left ventricular (LV) mass index (42.1 ± 9.9 g/m2.7 vs. 37.3 ± 8.0 g/m2.7, p = 0.004), while age, sex, prevalence of hypertension, diabetes, calcium score and positive remodelling did not differ between the groups (all p > 0.05). In multivariable regression analysis, total plaque burden remained associated with presence of myocardial ischemia (OR 1.02, 95% CI 1.00-1.04, p = 0.045) independent of age, sex, hypertension, diabetes, LV mass index, coronary calcium score and positive remodelling. CONCLUSION: Total coronary artery plaque burden by CCTA was independently associated with myocardial ischemia in patients with non-obstructive CAD. Whether plaque quantification is useful for clinical management of patients with non-obstructive CAD should be tested in prospective studies.ClinicalTrials.gov: Identifier NCT01853527.

Quantified coronary total plaque volume from computed tomography angiography provides superior 10-year risk stratification.

AIMS: Automated coronary total plaque volume (TPV) quantification derived from coronary computed tomographic angiography (CTA) datasets provide exact and reliable assessment of calcified and non-calcified coronary atherosclerosis burden. The aim of this analysis was to investigate the long-term predictive value of TPV. METHODS AND RESULTS: TPV was quantified in 1577 patients undergoing coronary CTA and cardiovascular events were collected during 10.5 years (interquartile range 6.0-11.4) of follow-up. The study endpoint comprised cardiac death and acute coronary syndrome and occurred in 59 (3.7%) patients. Coronary TPV provided additive prognostic value over clinical risk assessed with the Morise Score and coronary artery disease severity (rise in C-index from 0.744 to 0.769, P = 0.03). A category-based reclassification approach combining the Morise Score and TPV revealed superior risk stratification (categorical net reclassification improvement: 0.48 with 95% CI 0.13-0.68, P < 0.001) and resulted in reclassification of 800 (51%) patients compared with the Morise Score alone. The 10-year risk for the study endpoint was 0.6% (95% CI 0-1.3) for patients classified as low risk (n = 807), 4.8% (95% CI 2.4-7.2) for patients at intermediate risk (n = 400), and 10.3% (95% CI 6.6-13.9) for patients at high risk (n = 370) using the combined reclassification approach. CONCLUSION: Quantification of TPV from coronary CTA permits an improved 10-year cardiovascular risk stratification.

Coronary plaque burden of the left anterior descending artery in patients with or without myocardial bridge: A case-control study based on coronary CT-angiography.

BACKGROUND: The clinical significance of myocardial bridging (MB) on the left anterior descending artery (LAD) is debated. We aimed to assess the association between MB and LAD plaque volumes/compositions in a case-control set up. METHODS: In our retrospective analysis we investigated 50 cases with incidentally recognized LAD MB and 50 matched controls without LAD MB on coronary computed tomography angiography. We quantified plaque volumes proximal to the MB and beneath it in patients with MB and in the corresponding coronary segments in patients without MB. RESULTS: In total, we have included 100 patients (mean age 60.6 ± 10.8 years, males: 80%). Plaque volume was similar in the LAD segments proximal to the MB in cases vs. controls (150.0 mm3 [IQR: 90.7-194.5 mm3] vs. 132.8 mm3 [IQR: 94.2-184.3 mm3], respectively; p = 0.95) while the plaque volume was smaller beneath LAD MB vs. control segment (16.2 mm3 [IQR: 12.6-25.8 mm3] vs. 21.1 mm3 [IQR: 14.0-42.4 mm3], respectively; p = 0.002). No significant differences were found regarding different plaque components in segments proximal to the MB while fatty plaque and necrotic core volumes were smaller or negligible in coronary segment beneath MB than in controls (0.07 mm3 [IQR: 0.005-0.27 mm3] vs. 12.7 mm3 [IQR: 7.4-24.4 mm3] and 0.00 mm3 [IQR: 0.00-0.04 mm3] vs. 0.06 mm3 [IQR: 0.03-2.8 mm3], respectively (p < 0.001). CONCLUSION: Comparing patients with MB vs. matched controls without it, MB was not associated with increased plaque volumes in LAD segment proximal to MB and plaque quantity was smaller in the MB segment. Our data are supportive of benign nature of incidentally recognized LAD MB.

Coronary plaque volume and predictors for fast plaque progression assessed by serial coronary CT angiography-A single-center observational study.

PURPOSE: The rationale of this study was to identify patients with fast progression of coronary plaque volume PV and characterize changes in PV and plaque components over time. METHOD: Total PV (TPV) was measured in 350 patients undergoing serial coronary computed tomography angiography (median scan interval 3.6 years) using semi-automated software. Plaque morphology was assessed based on attenuation values and stratified into calcified, fibrous, fibrous-fatty and low-attenuation PV for volumetric measurements. Every plaque was additionally classified as either calcified, partially calcified or non-calcified. RESULTS: In total, 812 and 955 plaques were detected in the first and second scan. Mean TPV increase was 20 % on a per-patient base (51.3 mm³ [interquartile range (IQR): 14.4, 126.7] vs. 61.6 mm³ [IQR: 16.7, 170.0]). TPV increase was driven by calcified PV (first scan: 7.6 mm³ [IQR: 0.2, 33.6] vs. second scan: 16.6 mm³ [IQR: 1.8, 62.1], p < 0.01). Forty-two patients showed fast progression of TPV, defined as >1.3 mm3 increase of TPV per month. Male sex (odds ratio 3.1, p = 0.02) and typical angina (odds ratio 3.95, p = 0.03) were identified as risk factors for fast TPV progression, while high-density lipoprotein cholesterol had a protective effect (odds ratio per 10 mg/dl increase of HDL cholesterol: 0.72, p < 0.01). Progression to >50 % stenosis at follow-up was observed in 34 of 327 (10.4 %) calcified plaques, in 13 of 401 (3.2 %) partially calcified plaques and 2 of 221 (0.9 %) non-calcified plaques (p < 0.01). CONCLUSION: Fast plaque progression was observed in male patients and patients with typical angina. High HDL cholesterol showed a protective effect.

Plaque quantification by coronary computed tomography angiography using intravascular ultrasound as a reference standard: a comparison between standard and last generation computed tomography scanners.

AIMS: The emerging role of coronary computed tomography angiography (CCTA) as a non-invasive tool for atherosclerosis evaluation is supported by data reporting a good correlation between CCTA and intravascular ultrasound (IVUS) for plaque volume quantification. Aim of the present study was to evaluate whether a last generation CT-scanner may improve coronary plaque volume assessment using IVUS as standard-of-reference. METHODS AND RESULTS: From a registry of 1915 consecutive, all-comers, patients who underwent a clinically indicated IVUS evaluation we enrolled 59 patients who underwent CCTA with a 64-slice CT (Group 1) and 59 patients who underwent CCTA with whole-heart coverage CT scanner (Group 2). Patients who underwent CCTA with unfavourable heart rhythm were not excluded from the analysis. Image quality (4-point Likert scale) focused on plaque analysis was evaluated. Plaque volume quantification by CCTA was compared to IVUS. No difference in clinical characteristics was found between Group 1 and Group 2. Plaque volume quantification by CCTA was considered not feasible in 11 plaques of Group 1 and in 4 plaques of Group 2 (P = 0.09). Higher correlation for plaque volume quantification by CCTA vs. IVUS was demonstrated in Group 2 when compared with Group 1 (r = 0.9888 vs. 0.9499; P < 0.0001). The Bland-Altman analysis showed plaque volume overestimation by CCTA of 11.9 mm3 in Group 1 and 4 mm2 in Group 2 (P < 0.001). Effective radiation dose of CCTA was significantly lower in Group 2 vs. Group 1 (2.7 ± 0.9 vs. 8.1 ± 3.6 mSv, respectively; P < 0.001). CONCLUSIONS: CCTA using a new scanner generation showed to be an accurate non-invasive tool to assess and quantify coronary plaque volume.

Quantification of coronary low-attenuation plaque volume for long-term prediction of cardiac events and reclassification of patients.

BACKGROUND: To investigate the incremental prognostic value of low-attenuation plaque volume (LAPV) from coronary CT angiography datasets. METHODS: Quantification of LAPV was performed using dedicated software equipped with an adaptive plaque tissue algorithm in 1577 patients with suspected CAD. A combination of death and acute coronary syndrome was defined as primary endpoint. To assess the incremental prognostic value of LAPV, parameters were added to a baseline model including clinical risk and obstructive coronary artery disease (CAD), a baseline model including clinical risk and calcium scoring (CACS) and a baseline model including clinical risk and segment involvement score (SIS). RESULTS: Patients were followed for 5.5 years either by telephone contact, mail or clinical visits. The primary endpoint occurred in 30 patients. Quantified LAPV provided incremental prognostic information beyond clinical risk and obstructive CAD (c-index 0.701 vs. 0.767, p < .001), clinical risk and CACS (c-index 0.722 vs. 0.771, p < .01) and clinical risk and SIS (c-index 0.735 vs. 0.771, p < .01. A combined approach using quantified LAPV and clinical risk significantly improved the stratification of patients into different risk categories compared to clinical risk alone (categorical net reclassification index 0.69 with 95% CI 0.27 and 0.96, p < .001). The combined approach classified 846 (53.6%) patients as low risk (annual event rate 0.04%), 439 (27.8%) patients as intermediate risk (annual event rate 0.5%) and 292 (18.5%) patients as high risk (annual event rate 0.99%). CONCLUSION: Quantification of LAPV provides incremental prognostic information beyond established CT risk patterns and permits improved stratification of patients into different risk categories.

Impact of combined lipid lowering and blood pressure control on coronary plaque: myocardial ischemia treated by percutaneous coronary intervention and plaque regression by lipid lowering and blood pressure controlling assessed by intravascular ultrasonography (MILLION) study.

The aim of the study was to elucidate the aggressive reduction of both low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) reduced coronary atherosclerotic plaque volume compared with a standard treatment of LDL-C and BP in Japanese patients with coronary artery disease (CAD). This study is a prospective, randomized, and open-labelled with a blind-endpoint evaluation study. A total of 97 patients (81 men, mean age 62.0 ± 9.6) with CAD undergoing intravascular ultrasonography (IVUS)-guided percutaneous coronary intervention (PCI) were randomized, and 68 patients had IVUS examinations at baseline and at 18-24 months follow-up. Patients were randomly assigned to standard or aggressive strategies targeting LDL-C and a BP of 100 mg/dL and 140/90 mmHg vs. 70 mg/dL and 120/70 mmHg, respectively. The primary endpoint was the percent change in coronary plaque volume. Both standard and aggressive strategies succeeded to achieve target levels of LDL-C and BP; 74.9 ± 14.7 vs. 63.7 ± 11.9 mg/dL (NS) and 124.1 ± 9.4/75.8 ± 7.7 vs. 113.6 ± 9.6/65.8 ± 9.4 mmHg (systolic BP; NS, diastolic BP; p < 0.05), respectively. Both groups showed a significant reduction in the coronary plaque volume of -9.4 ± 10.7% and -8.7 ± 8.6% (NS) in standard and aggressive therapies, respectively. Both standard and aggressive intervention significantly regressed coronary plaque volume by the same degree, suggesting the importance of simultaneous reductions of LDL-C and BP for prevention of CAD.

Impact of combined lipid lowering with blood pressure control on coronary plaque regression: rationale and design of MILLION study.

A line of epidemiological studies suggests that the accumulation of coronary risk factors promotes the progression of coronary atherosclerosis. Recent clinical studies showed that aggressive low-density lipoprotein (LDL) cholesterol-lowering therapy using statins could regress coronary atheroma and reduce major cardiovascular events. Additionally, therapy that controlled amlodipine-based blood pressure reduced major cardiovascular events in patients with hypertension compared with an atenolol-based regimen. An open-label randomized multicenter study is primarily planned to evaluate the changes in coronary atheroma volume using intravascular ultrasonography 18-24 months after intensive lowering of LDL-cholesterol and blood pressure compared with a standard therapy indicated by current guidelines in Japanese patients with coronary artery disease (CAD). The secondary endpoints include changes in serum lipid levels, inflammatory markers, glucose markers and blood pressure. In total, 100 subjects with CAD who are undergoing percutaneous coronary intervention will be tested. The MILLION study will provide new evidence and therapeutic standards for the prevention of CAD in Japanese patients by controlling both LDL-C levels and blood pressure.